The following is an extract from an article in the SAMJ, Vol. 62,
p576-580, October,1982
by James H. S. Gear et al.

Congo-Crimean haemorrhagic fever

Congo-Crimean haemorrhagic fever was first observed in the Crimea by Russian
scientists in 1944 and 1945. At that time it was established by studies in human
volunteers that the aetiological agent was filtrable and that the disease in man
was associated with the bite of the tick Hyalomma marginatum. The agent
was detected in the larvae and in adult ticks, as well as in the blood of
patients during the fever. This agent, presumably a virus, was not maintained in
the laboratory and was lost.
Congo virus was first isolated in Africa from the blood of a febrile patient in
Zaire in 1956. In 1967 Simpson et al. described 12 cases of a feverish
illness of which 5 were laboratory infections; the virus was isolated by the
inoculation of blood into newborn mice. Simpson showed that these viruses were
similar to the one isolated in 1956. Casals then showed that the viruses
isolated in cases of Crimean haemorrhagic fever and the Congo virus were
serologically indistinguishable and demonstrated that other virus strains from
Central Asia, the USSR and Bulgaria were similar.
The virus has been classified as a Nairovirus in the genus Bunyavirus in
the family Bunyaviridae. It contains RNA and is inactivated by lipid solvents
and detergents.
Laboratory studies have shown that Congo virus is related to Hazara virus
isolated from ticks in Pakistan, and to Nairobi sheep disease virus; together
they form the Nairovirus group.
In Africa the virus has been isolated from a variety of animals, including
cattle, sheep, goats, hares and hedgehogs, and from a number of ticks which
parasitize them, including Hyalomma sp., Amblyomma variegatum,
Boophilus decoloratus and Rhipicephalus sp.

The most important transmitters of the infection
to man are species of the genus Hyalomma, the life history of which is
shown in the figure below.

The larval and nymphal stages of some species parasitize birds, including
migratory birds, some of which fly from south-eastern Europe to South Africa and
thus may carry the infection over long distances. To verify whether this
actually happens will require further study of the ticks and their hosts in
South Africa and on their way from Europe.

Clinical picture

The infection is usually transmitted to man by the bite of a tick, but an
increasing number of cases have occurred among the medical and nursing staff
caring for patients in hospital and in laboratory personnel carrying out
investigations of these patients. In these cases the infection has apparently
been acquired by contagion, particularly by contact with the patient's blood or
blood-contaminated specimens. Exposure to the blood of infected animals,
especially cattle and sheep, has led to severe and often fatal infections.

The incubation period is 2 - 7 days. The onset of the illness is sudden, with
fever, chills, severe muscular pains, headache, vomiting and pain in the
epigastric and lumbar regions. A haemorrhagic state develops from the 3rd to the
5th day and manifests as petechial haemorrhages or purpura in the skin, and
bleeding from the mucous membranes manifests as epistaxis, haemoptysis,
haematemesis, melaena and haematuria. At this stage the conjunctivae are
injected, the face is flushed and the tongue is dry, often coated with dry
blood. The pulse is slow in the beginning, but with continuing loss of blood
becomes fast and feeble; the blood pressure drops and the heart sounds become
weak - clear signs of impending shock and vascular collapse. The liver is
enlarged and tender and there is tenderness over the epigastrium and splenic
region. In patients who recover, the temperature falls between the 10th and the
20th day and bleeding stops, but convalescence is prolonged up to 4 weeks or
longer. In fatal cases, death from massive haemorrhage and cardiac arrest
occurs, usually 7 - 9 days after the onset of the illness. Massive haemorrhage
into the gastro-intestinal tract, with scattered haemorrhages into the viscera,
is found at autopsy.

The diagnosis is suggested on clinical grounds when the patient has a history
of a tick bite or of exposure to ticks in the environment, and after an
incubation period of 2 - 7 days develops an illness of sudden onset of muscle
pains, headache fever and a rapidly evolving severe illness with the development
of a haemorrhagic state with bleeding from the mucous membranes and petechiae in
the skin, associated with thrombocytopenia and leucopenia.
The diagnosis may be confirmed in the laboratory by intracerebral inoculation of
baby mice with blood of a patient; the mice sicken about 1 week after
inoculation. The virus is identified by using known specific Congo virus
antiserum in an immunofluorescent test. The development of antibodies in
patients' serum as the illness progresses may be demonstrated in
immunofluorescent tests using chamber slides with tissue culture cells infected
with Congo virus.

The authors are grateful to Professor 0. W. Prozesky, Director
of the National Institute for Virology, and to Dr R. Swanepoel, Dr K. Struthers,
Mrs E. Rossouw and Miss G. McGillivray, staff members of the high-security
laboratory, and to Dr P. Jupp of the Arbovirus Unit of the National Institute
for Virology for undertaking, as a matter of urgency, the investigations which
led to the incrimination of the Congo virus as the cause of this patient's fatal
illness. The authors are grateful to Mrs M. Anderson, who prepared the chart of
its life cycle.

This document was prepared by Professor Robert Swanepoel, and sent to the
listserv "Promed" at the end of the out break.

Hi Dr Woodall

Sorry I have not been feeding you the latest news on the outbreak but:

we are not exactly at the frontline although we are responsible for
laboratory confirmation of the diagnoses - I imply that there is a great deal
of sorting out of the "worried well" and that sort of thing going on, and as
the dust settles a clearer picture is beginning to emerge, and we are moving
over into a more investigative mode regarding the epidemiology of what exactly
went on.

I have my hands more than full dealing with local media and journalists,
and

as I said to you in another context, I shy away from public debate on the
internet in order to hide my ignorance.

Anyhow, now that you have asked I can answer the question about "bont" and
give you some sort of update on the outbreak. Bont means multicoloured or
variegated, and refers to the reddish-brown and white bands on the legs of ticks
of the genus Hyalomma. Ticks of the genus Amblyomma resemble Hyalommas in some
ways: they are of similar large size (relative to other ixodids), and have
similar bands on the legs, but Amblyommas are altogether more ornate, with
beautiful enamelling or metallic colours on the scutum, to gladden the heart of
the most jaded acarologist. There is also a single (sub)species of the genus
Rhipicephalus which can be confused with Hyalommas by the uninitiated:
Rhipicephalus evertsi mimeticus - the mimeticus part refers to the fact that it
mimics Hyalommas in having the banded leg ornamentation, but it lacks the
relatively long mouth parts of Hyalommas, Amblyommas, or even Aponommas (you
asked!).

The late Harry Hoogstraal in his extensive reviews of the literature made
reference to the fact that the world distribution of CCHF virus coincides pretty
well with the distribution of Hyalomma ticks (Africa, eastern Europe and Asia),
and indeed this became even more true after his last review as we found that the
virus occurs down the length of Africa, and it was likewise found to occur
across Asia to China (note, I did not say that the distribution has extended, or
that the virus has spread etc - only our knowledge of it). Other ticks can
transmit, but there seems to be a particular link with Hyalommas, and this has
certain epidemiologic consequences, relating for instance to the host
preferences of the immature and adult ticks, which differ from ticks of other
genera: larvae and nymphs feed on small mammals up to hare size and
ground-frequenting birds, while adults prefer large animals, the larger the
better. This means humans are not bitten by the immatures ("seed" or "pepper"
ticks) of Hyalommas (humans are bitten by the immatures of other ticks) and even
the adults are not that partial to humans, although they do bite if given good
reason. If this all were otherwise, and Hyalommas loved feeding on humans, we
would be in a sorry mess for antibody surveys on livestock sera show that we
live in a sea of CCHF virus within the distribution range of Hyalommas, and the
miracle is that there are so few human cases, not that there are so many.

Humans gain infection from tick bite (yes, the occasional Hyalomma), or from
contact of infected fresh blood (or other tissues) with broken skin - with the
infected blood/tissues coming either from human patients (nosocomial infections
- needle sticks etc), or other animals, commonly sheep and cattle. To our
knowledge, only humans and newborn mice readily succumb to disease; other
animals including nonhuman primates are either refractory or undergo mild
infection, sometimes with transient viraemia - including sheep and cattle (our
unpublished results). Sheep and cattle are viraemic for up to about a week, and
often exposure to ticks and virus infection occur at an early age, when farmers
may castrate, dehorn, stick in ear tags or immunize the young animals, and thus
expose themselves through getting infected blood onto broken skin. Sometimes
animals meet tick infestation for the first time late in life and then succumb
to tick-borne diseases of livestock such as babesiosis or anaplasmosis, at the
same time that they happen to have first met CCHF virus, and are thus viraemic
at a time when they are treated, autopsied, or even butchered by farmers,
veterinarians or farm workers respectively, and this constitutes another type of
incident leading to common source outbreaks. Most often then, the disease
affects stockmen and other farm dwellers, and townspeople only become infected
when they visit the countryside and get tick bite, or hunt and slaughter animals
etc. It is also enough to squash infected ticks with bare fingers - one does not
have to be bitten. The only town dwellers who are regularly exposed to infection
are slaughtermen at abbatoirs - since they encounter fresh blood and other
tissues of livestock (commonly sheep and cattle) hundreds of times daily -
sometimes more than a thousand head of sheep or cattle a day, they must come
across animals in the short viraemic phase of infection fairly often, and we
know they get the disease more frequently than other people, and it seems, also
relatively mild/silent infections with seroconversion - all the same, there
would probably be many more abbatoir infections if the viraemia in livestock
were more intense than it is - very low-titered in comparison with Rift Valley
fever for instance. Ticks which detach from hides and skins at slaughterhouses
after their engorgement has been so rudely interrupted, will sometimes attach to
whatever is available, and this constitutes another hazard for abbatoir workers.

What then of risk for the urban consumer of meat? In 17 years of looking at
about 2000 cases of suspected viral haemorrhagic fever, we have never found CCHF
in a town dweller who did not have a history of recent tick bite, or animal
blood contact in the countryside or at an abbatoir, nor were we able to isolate
virus from meat from experimentally infected sheep killed in viraemia. The virus
is not very resistant to heat and pH extremes etc, and we assume the fall in pH
associated with "maturation" of meat by hanging of carcases after slaughter, is
sufficient to put paid to residual virus after "bleeding out" of the animal at
slaughter.

Having said all that, we come to Oudtshoorn, the centre of an ostrich
industry which sells (locally and abroad), feathers, skins and meat. An ostrich
farmers' co-operative runs several slaughterhouses, and these resumed
slaughtering (after an off season) on 21 October. (Two of the abbatoirs are in
Oudtshoorn.) By pure coincidence a survey was undertaken at the largest of the
abbatoirs of the tick burden (mainly Hyalomma truncatum) on birds coming in from
various farms, and it was found that six consignments were heavily infested.
This is the slaughterhouse where the outbreak occurred. As far as I know at
present - and the dust has not yet settled properly - abbatoir workers started
becoming ill from about Sunday 27 October to Wednesday 30, and being admitted to
Oudtshoorn Hospital from Thursday 31 to Saturday 2 November, and on Sunday 3
November four patients were transferred to Tygerberg Hospital, Bellville, near
Cape Town. We received serum samples from these four on Monday 4 November
afternoon, and that evening confirmed that three had IgG and IgM antibodies to
CCHF virus, and that the fourth was PCR positive for viral nucleic acid.
Meantime media hysteria mounted and, I think, hundreds of worried folk presented
with varying degrees of "symptoms" - I think there are something like 350
workers at the abbatoir, but all will be known later. Various people were
admitted to Oudtshoorn, including a forty six year old lady who died on Monday 4
November (she was an abbatoir worker and has been cremated) - we received only
formalin fixed bits of liver taken with a biopsy needle - this was last night
(Wed 6 Nov) and we are awaiting preparation of histo sections to perform
immunocytochemical staining.

Meantime a further 12 or so patients were transferred to Tygerberg, I think
Tues evening, and we received serum samples from 13 patients (over and above
repeat bleeds on the original four) last night and this afternoon. Of these
thirteen, 11 were IgG and IgM positive, and two negative for antibody and PCR
(one of these was not really a patient - simply an abbatoir worker who pitched
up at hospital to visit somebody else and was bled for her troubles). So, Dr
Mark Beale at Tygerberg Hospital who is in over all control of the clinical side
of things, and his supporting workers at both centres, seem to have done a very
good job of sorting the sheep from the goats, and the fourteen antibody positive
patients are to be discharged tomorrow (Friday 8 Nov). The original PCR positive
patient who lacked antibodies remains PCR positive, antibody negative, and still
has low platelets, but seems well. He will be detained in Tygerberg for the
meantime, as will one of the two PCR and antibody negative people who seems
quite ill (the other was the hospital visitor who was not ill or admitted). All
of the above patients were abbatoir workers. I am not sure who remains in
Oudtshoorn Hospital, but there are two children from whom we await specimens -
one is, and both may be, children of abbatoir workers, and it is thought that
one in fact has hepatitis A (or B?).

All of the abbatoirs were closed and we are approaching the end of the
theoretical incubation period when we can expect further primary common source
cases - there appear to have been no secondary (human-to-human cases) unless
either or both of the two children prove to be cases. It will take a further
while to make virus isolations, but antibody detection and PCR have done a
splendid job of rapid laboratory confirmation for us. To summarize: 14
seropositive patients are all well, and ready to be discharged; one deceased
probable case is still to be confirmed by immunocytochemistry, one PCR positive
antibody negative patient is off the critical list but still in hospital, and
one PCR negative and antibody negative patient (who may or may not prove to be a
case) is still in hospital, as are two children. Excluding the children, 10 of
the patients are female (including the deceased), and most are young adults -
the high proportion of females relates to the fact that many females are
employed in the ostrich abbatoirs as compared to sheep and cattle abbatoirs.

Prof James Joubert at Tygerberg Hospital has arranged for Dr Neil du Toit,
seconded form Tygerberg, to bleed (subject to necessary consent etc) all
abbatoir workers and we shall test for evidence of mild, or past, or inapparent
infections. I have advised that farmers should have a section of their feedlots
double fenced, the inner fence to be small animal proof, and that ostriches
should be treated with a short half life pyrethroid acaricide (non residual) 14
days before being sent for slaughter and placed in the fenced off "quarantine"
section for this period - they should then arrive at the slaughterhouse tick and
virus and acaricide free, by analogy with sheep and cattle experiments, but we
still have to do ostrich experiments. Pyrethroids in any event have very rapid
"knockdown" (lethal) effect on ticks, and very low mammalian toxicity. The
Directorate of Veterinary Public Health and ostrich farmers' co-ops and research
organizations have met to discuss the problem, and will act something on the
lines I have suggested. Meanwhile Dr Willem Burger of the ostrich producers
research lab has sent us ten half grown chicks (tick free) to do experimental
viraemia studies etc (they are big enough to look you in the eye, and they
defaecate a bucketful - any volunteers to help us?) I shall be visiting the area
hopefully next week and with Dr Burger visit farms to collect ticks etc. From
our sheep and cattle surveys we know that the virus is everywhere, and while we
are not trying to incriminate anybody, it will be interesting to see if we can
get virus isolates from ticks to match up by nucleotide sequencing with any
isolates from patients. (The fact that most infections have been relatively
benign is interesting of itself).

Incidentally, there was a worker at an ostrich slaughterhouse near Oudtshoorn
who became infected in 1984 - he claimed that Hyalomma ticks on ostriches
scratched his hands and arms as he pulled off the skins from the birds, and we
thought that was one possible way of becoming infected. Another would be ticks
transferring to the slaughtermen after detachment from ostrich skins, and of
course, another possibility is that ostriches can become viraemic - which we are
setting out to investigate now. We previously failed to obtain ostriches to
experiment on, and tested guinea fowl and chickens - which were fairly resistant
to the virus - but they may be quite different from ostriches which, I think,
may have a slightly different thermoregulatory capacity from other birds, for
one thing.